Synthesis and biological activities of 2-Methyl-4-N-2-cyanoethyl-N-substituted benzaldehydes and their derivatives
Y.K. Gupta1*, S.C. Agarwal2, Dilip Sharma3
1Head Department of Chemistry, B K Birla Institute of Engineering and Technology, Pilani, Rajasthan, India
2Head Department of Chemistry, Agra College, Agra, U.P, India
3Department of Chemistry, Agra College, Agra, U.P, India
*Corresponding Author E-mail: ykgbkbiet@rediffmail.com, ykgbkbiet@yahoo.com, ykgbkbiet123@gmail.com
ABSTRACT:
Synthesis and antibacterial, antitubercular, anticancer, anti AIDS and fungicidal activities of 2-methyl-4-N-2-cyanoethyl-N-methane/benzenesulphonylaminobenzaldehyde and their Hydrazones are reported.
INTRODUCTION:
Tertiary amino benzaldehydes are important due to the role in the synthesis of chemotherapeutics1,2 and analytical reagents 3. Acid hydrazones derived from aldehydes have shown antitubercular4, fungicidal5 activities. The utility of acid hydrazones, we report here synthesis of some titled benzaldehydes and their acid hydrazones which bear 1,3-diketoamino structural feature analogues to pyrimidine bases as potential biomimetics.
m-Toluidine on monocyanoethylation6 in presence of cupric acetate gave N-2-cyanoethyl-mtoluidine. Reaction of the later with the methane sulphonyl chloride or benzene sulphonyl chloride in presence of sodium hydroxide gave two tertiary amines: (1) N-2-cyanoethyl-Nmethanesulphonyl- m-toluidine and (2) N-2-cyanoethyl-Nbenzenesul phonyl-m-toluidine formylation of these two sulphonyl toluidine using DMF/POCl3 gave 2-methyl-4-N-2- cyanoethyl-N-methanesulphonylaminobenzaldehyde (3) and 2-methyl-4-N-2-cyanoethyl-N-benzenesulphonyl aminobenzaldehyde (4). Condensation of the new aldehydes (3, 4) with malonanilic acid hydrazides7,8 furnished malonanilic acid hydrazones (5a–j, 6a–j) in yield ranging from 55% to 79% (Scheme 1)
Structure of the new products was confirmed by elemental analysis and spectral data
(Scheme 1)
EXPERIMENTAL:
All melting points are uncorrected. The IR spectra were taken on the Perkin Elmer-577 model spectrometer and elemental analysis was carried out by CEST-110 model.
4-N-2-Cyanoethyl-N-methanesulphonyl-m-toluidine
A mixture of 4-N-2-cyanoethyl-m-toluidine (1.5 g, 0.01 mol) and aqueous sodium hydroxide (5 ml, 10%) was heated on boiling water bath methane sulphonyl chloride (3 ml) was added with constant stirring when a solid was obtained as white crystals (73%); m.p. 75 0C; (Found: C, 59.19; H, 5.34; N, 10.72; S, 12.26% C11H14N2O2S requires: C, 59.23; H, 5.38; N, 10.76; S, 12.30%); mmax (KBr) 1070 (–SO2), 1330 (–N<), 1445 (>CH2), 1470 (–CH3), and 2220 cm-1 (–C„N). The other compound 2 were prepared following similar procedure.
2-Methyl-4-N-2-cyanoethyl-Nmethanesulphonylaminobenzaldehyde
4-N-2-cyanoethyl-N-methanesulphonyl-m-toludine (15.47 g, 0.068 mol) was cooled in ice bath (0–10 0C). The contents were stirred and a mixture of phosphorous oxychloride (11.2 g, 0.072 mol) and DMF (18.4 g, 0.252 mol) was added drop wise during the course of reaction. The reaction mixture was heated for three hours on a boiling water bath. The contents were, cooled; crushed ice was added followed by sodium acetate (50 g), when solid product was obtained. The product on recrystallisation from ethanol yielded fine white crystals (37%), M.P. 950C, (Found: C, 57.90; H, 4.79; N, 9.62; S, 11.01% C12H14O3N2S requires: C, 57.93; H, 4.82; N, 9.65; S, 11.03%). mmax (KBr) 1050 (–SO2), 1350 (–N<), 1450 (>CH2), 1580 (C–CHO) and 2220 cm-1 (–C,N).
2-Methyl-4-N-2-cyanoethyl-N-benzenesulphonylaminobenzaldehyde (4) was prepared by similar procedure.
2-Methyl-4-N-2-cyanoethyl-N-methanesulphonylaminobenzaldehydeanilinomalonyl - hydrazone (5a)
Ethanol was added to a solution of 2-methyl-4-N-20-cyanoethyl-N-methanesulphonylamino- benzaldehyde (0.290 g 0.001 mol) in ethanol (5 ml) a solution of malonanilic acid hydrazide (0.196 g, 0.001 mol). The contents were warmed, left aside for 2 hr. when the acid hydrazone separated. It was collected under suction and recrystallised from rectified spirit as pale yellow crystals, (58%), M.P. 1130C, (found: C, 60.10; H, 4.72; N, 14.44; S, 6.80% C21H23N5O4S requires: C, 60.13; H, 4.76; N, 14.49; S, 6.83%). mmax (KBr): 1060 (–SO2), 1320 (–N<), 1705 (>C‚O), 1780 (–CH2) and 2220 cm-1 (–C„N). All other acid hydrazones were prepared by the aforementioned procedure; physical data of these compounds are given in Table 1.
Table 1 Physical data of the acid hydrazones.
|
Compd. No. |
R2 |
M.P. (0C) |
Yield (%) |
Mol. formula |
|
5a |
H |
113 |
58 |
C21H23O4N5S |
|
5b |
Me (2) |
120 |
66 |
C22H25O4N5S |
|
5c |
Me (3) |
100 |
62 |
C22H25O4N5S |
|
5d |
Me (4) |
110 |
73 |
C22H25O4N5S |
|
5e |
Cl (2) |
103 |
68 |
C21H22O4N5SCl |
|
5f |
Cl (3) |
105 |
63 |
C21H22O4N5SCl |
|
5g |
Cl (4) |
106 |
70 |
C21H22O4N5SCl |
|
5h |
OMe (2) |
110 |
63 |
C22H25O5N5S |
|
5i |
OMe (3) |
102 |
62 |
C22H25O5N5S |
|
5j |
OMe (4) |
111 |
67 |
C22H25O5N5S |
|
6a |
H |
109 |
58 |
C26H25O5N5S |
|
6b |
Me (2) |
140 |
62 |
C27H27O5N5S |
|
6c |
Me (3) |
108 |
57 |
C27H27O5N5S |
|
6d |
Me (4) |
107 |
62 |
C27H27O5N5S |
|
6e |
Cl (2) |
99 |
63 |
C26H24N5O4SCl |
|
6f |
Cl (3) |
95 |
57 |
C26H24N5O4SCl |
|
6g |
Cl (4) |
120 |
59 |
C26H24N5O4SCl |
|
6h |
OMe (2) |
116 |
55 |
C27H27N5O5S |
|
6i |
OMe (3) |
98 |
61 |
C27H27N5O5S |
|
6j |
OMe (4) |
117 |
63 |
C27H27N5O5S |
All the compounds gave satisfactory elemental analysis.
Biological activities
AntiHIV activity
The compounds 3, 4, 5h, 5j, 6f and 6j were screened for antiviral activity for AIDS, which involved susceptible human host cells. The response of the compounds on the infected plates was 11.67%, 6.67%, 22.23%, 23.15%, 20.09% and 19.18% respectively as compared to standard AZT.
AntiHIV activity of hydrazones 5h, 5j, 6f and 6j was found to be higher that of the corresponding aldehydes 3 and 4. The compounds 3, 4, 5h, 5j, 6f and 6j were tested for anticancer activity which involved different cell lines (lung, colon, malonoma, ovarian, renal). The compounds did not show significant anticancer activity.
Antitubercular activity
The compounds 3, 4, 5c, 5g, 6a and 6d were incorporated into Lowenstien–Jenson egg medium having concentration of 10 and 100 µg ml-1and were inoculated with Mycobocterium tuberculosis H37RV strain incubated at 37 0C and observed weekly for the growth of organism for eight weeks. The compounds were found to be inactive at the concentration used.
Antibacterial activity
The compounds 3, 4, 6f and 6j were tested for their antibacterial activity against gram positive Staphylococcus aureus and gram negative Escherichia coli bacteria using cup-plate method9. The% control was found in the range of 15–30%.
Fungicidal activity
The compounds 3, 4, 5i and 6g were evaluated by Agar plate food poisoning method10 in 500 and 1000 ppm concentrations. (Using P.D.A. medium). Plain medium was used as control; all compounds were found active (30–45%) against Alternaria alternata, Rhizopus arrhizus and Aspergillus niger at the concentrations tested.
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Received on 17.02.2012 Modified on 22.02.2012
Accepted on 28.02.2012 © AJRC All right reserved
Asian J. Research Chem. 5(2): February 2012; Page 245-247